Complement receptors CD21/CD35 provide an important link between innate and adaptive immunity by mediating the enhancing effects of complement on B cell activation and memory. On B cells CD21/CD35 form a co-receptor along with CD19 and CD81 ; whereas on follicular dendritic cells (FDC) they provide a mechanism for antigen retention. In both cases they serve to enhance the effects of antigen on the humoral response. The overall goal of this proposal is to clarify how complement receptors participate in the uptake, transport and deposition of antigen within the lymphoid compartment and to dissect the mechanism whereby they influence differentiation of activated B cells. Three aims are proposed: The first aim will examine the mechanism of uptake, transport and transfer of protein antigen onto FDC in peripheral lymph nodes. The second aim will test the hypothesis that follicular B cells form a synapse with FDCin vitro and vivo and that co-receptor signaling participates in antigen uptake. The third aim will test the hypothesis that the complement system participates in differentiation of GCB cells into antibody secreting cells (BASC) and memory Understanding how the complement system enhances trafficking and uptake of antigen within the lymphoid compartment and influences B cell differentiation into antibody secreting cells or memory cells is significant as it will not only extend our understanding of these processes but could be valuable in development of vaccination protocols.